The overall objective of the proposed research is to study the effects of opiate exposure of brain cells on their synthesis of cyclic nucleotides (cyclic AMP and cyclic GMP), prostaglandins (PGE2 and PGF2) and beta-endorphin. For these studies we will use a fetal rat brain culture system which has been extensively characterized in our laboratory for neurotransmitter metabolizing enzymes, neurotransmitter synthesis and morphological development. Recent preliminary data indicate that these cultures contain opiate receptors, synthesize prostaglandins (PGE-like and PGF-like immunoreactive material) and beta-endorphin (beta-endorphin-like immunoreactive material). Effects of opiates, their antagonists and inactive stereoisomers will be tested acutely, chronically and during withdrawal on the above stated biochemical parameters. Cell culture, radioligand binding assays and radioimmunoassays will be the techniques used. These studies may further our understanding about the biochemical correlates of drug addiction to opiates.